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Induction of apoptosis by chelerythrine chloride through mitochondrial pathway and Bcl-2 family proteins in human hepatoma SMMC-7721 Cell
Authors:Zheng-fu Zhang  Ying Guo  Jian-bin Zhang  Xiong-hui Wei
Institution:(1) International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, China;(2) Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China;(3) State Key Laboratory for Oncogenes and Related Genes, Cancer Institute of Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China
Abstract:The objective of this study was to evaluate the antitumor activity of chelerythrine chloride (CHE) and investigate its potential apoptotic induction mechanism in SMMC-7721 cells. Our results suggested that the proliferation of SMMC-7721 cells was inhibited by CHE in a time and dose dependent manner, with a significant accumulation in S phase, and the cells exhibited typical apoptotic features. Moreover, CHE remarkably induced apoptosis by disruption of the mitochondrial membrane potential, release of Cyt-c, activation of caspase-3, and cleavage of poly-ADP-ribose polymerase in a dose dependent manner. Furthermore, the expression of Bcl-xl was downregulated while Bax and Bid expression was upregulated, and no variation was found for Bcl-2. These results indicated that CHE may play an important role in suppression of tumor growth by inducing apoptosis in human hepatoma cells via the activation of a mitochondrial pathway and regulating the expression of Bcl-2 family proteins.
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